Functional properties of in vitro excitatory cortical neurons derived from human pluripotent stem cells

The in vitro derivation of regionally defined human neuron types from patient‐derived stem cells is now established as a resource to investigate human development and disease. Characterization of such neurons initially focused on the expression of developmentally regulated transcription factors and neural markers, in conjunction with the development of protocols to direct and chart the fate of differentiated neurons. However, crucial to the understanding and exploitation of this technology is to determine the degree to which neurons recapitulate the key functional features exhibited by their native counterparts, essential for determining their usefulness in modelling human physiology and disease in vitro. Here, we review the emerging data concerning functional properties of human pluripotent stem cell‐derived excitatory cortical neurons, in the context of both maturation and regional specificity. [Image: see text

Validation of Aura Microwave Limb Sounder O-3 and CO observations in the upper troposphere and lower stratosphere

International audienceGlobal satellite observations of ozone and carbon monoxide from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed with emphasis on those observations in the 215–100 hPa region (the upper troposphere and lower stratosphere). The precision, resolution and accuracy of the data produced by the MLS “version 2.2” processing algorithms are discussed and quantified. O3 accuracy is estimated at ~40 ppbv +5% (~20 ppbv +20% at 215 hPa) while the CO accuracy is estimated at ~30 ppbv +30% for pressures of 147 hPa and less. Comparisons with expectations and other observations show good agreements for the O3 product, generally consistent with the systematic errors quoted above. In the case of CO, a persistent factor of ~2 high bias is seen at 215 hPa. However, the morphology is shown to be realistic, consistent with raw MLS radiance data, and useful for scientific study. The MLS CO data at higher altitudes are shown to be consistent with other observations

The UARS microwave limb sounder version 5 data set: Theory, characterization, and validation

Nitric acid (HNO3) is a major player in processes controlling the springtime depletion of polar ozone. It is the main constituent of the Polar Stratospheric Clouds (PSCs) and a primary reservoir for reactive nitrogen. Potential variations in the stratospheric circulation and temperature may alter the extent and duration of PSCs activity, influencing the future ozone levels significantly. Monitoring HNO3 and its long-term variability, especially in polar region, is then crucial for better understanding issues related to ozone decline and expected recovery. In this study we present an intercomparison between ground based HNO3 measurements, carried out by means of the Ground-Based Millimeter-wave Spectrometer (GBMS), and two satellite data sets produced by the two NASA/JPL Microwave Limb Sounder (MLS) experiments. In particular, we compare UARS MLS measurements (1991-1999) with those carried out by the GBMS at South Pole, Antarctica (90°S), Fall of 1993 and 1995. A similar intercomparison is made between Aura MLS HNO3 observations (2004 - to date) and GBMS measurements obtained during the period February 2004 - March 2007, at the mid-latitudes/high altitudes station of Testa Grigia (45.9° N, 7.7° E, elev. 3500 m), and during polar winters 2008/09 and 2009/2010 at Thule Air Base (76.5°N 68.8°W), Greenland. We assess systematic differences between GBMS and both UARS and Aura HNO3 data sets at seven potential temperature levels (θ) spanning the range 465 – 960 K. The UARS data set advected to the South Pole shows a low bias, within 20% for all θ levels but the 960 K, with respect to GBMS measurements. A very good agreement, within 5%, is obtained between Aura and GBMS observations at Testa Grigia, while larger differences, possibly due to latitude dependent effects, are observed over Thule. These differences are under further investigations but a preliminary comparison over Thule among MLS v3, GBMS, and ACE-FTS measurements suggests that GBMS measurements carried out during winter 2009 might not be reliable. These comparisons have been performed in the framework of the NASA JPL GOZCARDS project, which is aimed at developing a long-term, global data record of the relevant stratospheric constituents in the context of ozone decline. GBMS has been selected in GOZCARDS since its HNO3 dataset, although sampling different latitudes in different years, is the only one spanning a sufficiently long time interval for cross-calibrating HNO3 measurements by the UARS and Aura MLS experiments

Repeatability of buried charge testing

The relationship between the geotechnical parameters and the impulse delivered by a charge buried shallowly (<100 mm) within a soil mass has received much attention in recent times. It has previously been demonstrated that for uniform soils a high degree of repeatability in the delivered impulse can be achieved when carefully controlling the geotechnical conditions. In this paper the authors explore the recommendations given in AEP55 regarding the testing of surrogate mine blasts using both minepots and the STANAG standard sandy gravel. With moisture content and bulk density being intrinsically coupled, using bulk density as a measure of geotechnical control and hence repeatability is questionable. A methodology for the careful preparation of the Stanag sandy gravel soil is presented along with comparative results from minepots demonstrating the comparative repeatability of both methodologies. These results are then compared with a number of other soils to allow gen-eral conclusions about the repeatability of specific soil characteristics to be drawn

Allele Copy Number and Underlying Pathology Are Associated with Subclinical Severity in Equine Type 1 Polysaccharide Storage Myopathy (PSSM1)

Equine type 1 polysaccharide storage myopathy (PSSM1), a common glycogenosis associated with an R309H founder mutation in the glycogen synthase 1 gene (GYS1), shares pathological features with several human myopathies. In common with related human disorders, the pathogenesis remains unclear in particular, the marked phenotypic variability between affected animals. Given that affected animals accumulate glycogen and alpha-crystalline polysaccharide within their muscles, it is possible that physical disruption associated with the presence of this material could exacerbate the phenotype. The aim of this study was to compare the histopathological changes in horses with PSSM1, and specifically, to investigate the hypothesis that the severity of underlying pathology, (e.g. vacuolation and inclusion formation) would (1) be higher in homozygotes than heterozygotes and (2) correlate with clinical severity. Resting and post-exercise plasma creatine kinase (CK) and aspartate aminotransferase (AST) enzyme activity measurements and muscle pathology were assessed in matched cohorts of PSSM1 homozygotes, heterozygotes or control horses. Median (interquartile range (IR)) resting CK activities were 364 (332–764) U/L for homozygotes, 301 (222–377) U/L for heterozygotes and 260 (216–320) U/L for controls, and mean (+/− SD) AST activity for homozygotes were 502 (+/116) U/L, for heterozygotes, 357 (+/−92) U/L and for controls, 311 (+/−64) U/L and were significantly different between groups (P = 0.04 and P = 0.01 respectively). Resting plasma AST activity was significantly associated with the severity of subsarcolemmal vacuolation (rho = 0.816; P = 0.01) and cytoplasmic inclusions (rho = 0.766; P = 0.01). There were fewer type 2× and more type 2a muscle fibres in PSSM1-affected horses. Our results indicate that PSSM1 has incomplete dominance. Furthermore, the association between plasma muscle enzyme activity and severity of underlying pathology suggests that physical disruption of myofibres may contribute to the myopathic phenotype. This work provides insight into PSSM1 pathogenesis and has implications for related human glycogenoses

The Carbon Monoxide Tape Recorder

Using Aura MLS data we have identified the stratospheric tape recorder in carbon monoxide (CO). Unlike the water vapor tape recorder, which is controlled by upper troposphere processes, the CO tape recorder is linked to seasonal biomass burning. Since CO has a lifetime of only a few months, the CO tape recorder barely extends above 20 km. The tape head for CO appears to be close to 360K near the same location as the water vapor tape head [Read et al, 20041. Both tape heads are below the equatorial cold point tropopause but above the base of the tropical tropopause layer. The tape recorder signal becomes more distinct from 360K to 380K suggesting that convective detrainment of plays a decreasingly important role with altitude. The Global Modeling Initiative chemical transport model forced by the climatology of biomass burning reproduces the CO tape recorder

The High Arctic in Extreme Winters: Vortex, Temperature, and MLS and ACE-FTS Trace Gas Evolution

The first three Canadian Arctic Atmospheric Chemistry Experiment (ACE) Validation Campaigns at Eureka (80° N, 86° W) were during two extremes of Arctic winter variability: Stratospheric sudden warmings (SSWs) in 2004 and 2006 were among the strongest, most prolonged on record; 2005 was a record cold winter. New satellite measurements from ACE-Fourier Transform Spectrometer (ACE-FTS), Sounding of the Atmosphere using Broadband Emission Radiometry, and Aura Microwave Limb Sounder (MLS), with meteorological analyses and Eureka lidar and radiosonde temperatures, are used to detail the meteorology in these winters, to demonstrate its influence on transport and chemistry, and to provide a context for interpretation of campaign observations. During the 2004 and 2006 SSWs, the vortex broke down throughout the stratosphere, reformed quickly in the upper stratosphere, and remained weak in the middle and lower stratosphere. The stratopause reformed at very high altitude, above where it could be accurately represented in the meteorological analyses. The 2004 and 2006 Eureka campaigns were during the recovery from the SSWs, with the redeveloping vortex over Eureka. 2005 was the coldest winter on record in the lower stratosphere, but with an early final warming in mid-March. The vortex was over Eureka at the start of the 2005 campaign, but moved away as it broke up. Disparate temperature profile structure and vortex evolution resulted in much lower (higher) temperatures in the upper (lower) stratosphere in 2004 and 2006 than in 2005. Satellite temperatures agree well with Eureka radiosondes, and with lidar data up to 50–60 km. Consistent with a strong, cold upper stratospheric vortex and enhanced radiative cooling after the SSWs, MLS and ACE-FTS trace gas measurements show strongly enhanced descent in the upper stratospheric vortex during the 2004 and 2006 Eureka campaigns compared to that in 2005